CN101218216A - Preparation of N-substituted isothiazolinone derivatives - Google Patents
Preparation of N-substituted isothiazolinone derivatives Download PDFInfo
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- CN101218216A CN101218216A CNA2006800247050A CN200680024705A CN101218216A CN 101218216 A CN101218216 A CN 101218216A CN A2006800247050 A CNA2006800247050 A CN A2006800247050A CN 200680024705 A CN200680024705 A CN 200680024705A CN 101218216 A CN101218216 A CN 101218216A
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- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- -1 N-substituted isothiazolinone Chemical class 0.000 title abstract description 19
- 150000001875 compounds Chemical class 0.000 claims abstract description 43
- 238000000034 method Methods 0.000 claims abstract description 36
- 239000002904 solvent Substances 0.000 claims abstract description 21
- 238000006243 chemical reaction Methods 0.000 claims description 28
- XTHPWXDJESJLNJ-UHFFFAOYSA-N sulfurochloridic acid Chemical compound OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 claims description 24
- 239000000460 chlorine Substances 0.000 claims description 15
- 229910052801 chlorine Inorganic materials 0.000 claims description 15
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 13
- 125000003118 aryl group Chemical group 0.000 claims description 13
- 150000001263 acyl chlorides Chemical class 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 125000004104 aryloxy group Chemical group 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- 230000001476 alcoholic effect Effects 0.000 claims description 4
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 abstract description 21
- 150000001412 amines Chemical class 0.000 abstract description 4
- 229910052757 nitrogen Inorganic materials 0.000 abstract description 4
- 150000004702 methyl esters Chemical class 0.000 abstract 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 abstract 1
- VUWCWMOCWKCZTA-UHFFFAOYSA-N 1,2-thiazol-4-one Chemical class O=C1CSN=C1 VUWCWMOCWKCZTA-UHFFFAOYSA-N 0.000 description 8
- 125000000217 alkyl group Chemical group 0.000 description 7
- 238000006467 substitution reaction Methods 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 239000003960 organic solvent Substances 0.000 description 6
- 239000004215 Carbon black (E152) Substances 0.000 description 5
- 229930195733 hydrocarbon Natural products 0.000 description 5
- 239000000376 reactant Substances 0.000 description 5
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 125000004119 disulfanediyl group Chemical group *SS* 0.000 description 4
- 239000012452 mother liquor Substances 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical group CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 3
- 125000000753 cycloalkyl group Chemical group 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 238000005660 chlorination reaction Methods 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- NIQCNGHVCWTJSM-UHFFFAOYSA-N dimethyl benzenedicarboxylate Natural products COC(=O)C1=CC=CC=C1C(=O)OC NIQCNGHVCWTJSM-UHFFFAOYSA-N 0.000 description 2
- FBSAITBEAPNWJG-UHFFFAOYSA-N dimethyl phthalate Natural products CC(=O)OC1=CC=CC=C1OC(C)=O FBSAITBEAPNWJG-UHFFFAOYSA-N 0.000 description 2
- 229960001826 dimethylphthalate Drugs 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 238000003912 environmental pollution Methods 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000010926 purge Methods 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- PWPGSMUAKWZWAE-UHFFFAOYSA-N 2-octyl-3h-1,2-thiazole Chemical compound CCCCCCCCN1CC=CS1 PWPGSMUAKWZWAE-UHFFFAOYSA-N 0.000 description 1
- GUUULVAMQJLDSY-UHFFFAOYSA-N 4,5-dihydro-1,2-thiazole Chemical compound C1CC=NS1 GUUULVAMQJLDSY-UHFFFAOYSA-N 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- GNDRGPOVANZJFN-UHFFFAOYSA-N N1=CC=CC2=CC=CC=C12.CN1SC=CC1 Chemical compound N1=CC=CC2=CC=CC=C12.CN1SC=CC1 GNDRGPOVANZJFN-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- MUCRYNWJQNHDJH-OADIDDRXSA-N Ursonic acid Chemical compound C1CC(=O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CC[C@@H](C)[C@H](C)[C@H]5C4=CC[C@@H]3[C@]21C MUCRYNWJQNHDJH-OADIDDRXSA-N 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 230000003373 anti-fouling effect Effects 0.000 description 1
- 239000002519 antifouling agent Substances 0.000 description 1
- 239000004035 construction material Substances 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 125000003963 dichloro group Chemical group Cl* 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- 239000000417 fungicide Substances 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 239000008235 industrial water Substances 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- IOQPZZOEVPZRBK-UHFFFAOYSA-N octan-1-amine Chemical compound CCCCCCCCN IOQPZZOEVPZRBK-UHFFFAOYSA-N 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 1
- 229940080818 propionamide Drugs 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 235000021003 saturated fats Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000009941 weaving Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
- C07D275/02—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings not condensed with other rings
- C07D275/03—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings not condensed with other rings with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/60—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton with the carbon atom of at least one of the carboxyl groups bound to nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Methods for the preparation of N-substituted isothiazolinone derivatives are provided, which include reacting the N-substituted 3-mercaptopropionamide of formula II or N,N'-disubstituted 3,3'-dithiadipropionamide with sulfurylchloride, in the absence of solvents. Methods for the preparation of compounds represented of formula III are also provided, which include reacting the methyl ester of formula IV with amine of formula V in the presence of methanol as solvent. The present methods need not use any other solvent, and therefore can lower the cost and reduce the pollution.
Description
The preparation of the isothiazolinone derivatives of N- substitutions
Technical field
The present invention relates to the preparation method of isothiazolinone derivatives, the preparation method of the isothiazolinone derivatives of more particularly to N- substitutions.Background technology
Isothiazolinone compound is the new high-effective broad-spectrum fungicide of a class, has the advantages that efficient, low toxicity, duration of efficacy length, environmental sound.Therefore it is widely used in the fields such as Treatment of Industrial Water, cosmetics, construction material, adhesive, coating, health care, weaving, photograph, detergent, especially can serve as the anti-fouling agent in marine antifouling coating.
So far, the method of the isothiazolinone derivatives for preparing N- substitutions reported in document is blunt more, but generally all include making Ν, Ν '-dibasic dithio dipropyl acidamide or Ν-substituted mercaptopropionyl amine in organic solvent with) change reagent reacting.
For example, Publication No. CN1634889 and CN1629148 Chinese patent application individually disclose Ν-alkoxy propyl iso thiazolinone and Ν-alcoxyl ethoxycarbonyl propyl isothiazole drenches the preparation method of ketone, including making corresponding Ν, Ν ,-dibasic dithio dipropyl acidamide reacts with chlorosulfuric acid in ethyl acetate. '
Publication No. JP 2003-335763 Japanese patent application discloses the preparation method for -4- isothiazoline -3- ketone for preparing 2- substitutions, mercaptopropionyl amine or Ν including making Ν-substituted, Ν,-dibasic dithio dipropyl acidamide in ethyl acetate solvent with) change reagent reacting.
The method for preparing 2- methyl-isothiazol quinoline -3- ketone is disclosed in European Patent Publication the 0498347th, including makes Ν-methyl -3- mercaptopropionyls amine in aromatic hydrocarbons or halogenated hydrocarbon solvent（Such as benzene, toluene, chlorobenzene, chloroform etc.) in chlorine reaction.
The method for preparing 2- alkyl -4- isothiazoline -3- ketone is disclosed in European Patent Publication the 1113012nd, including make Ν-alkylmercapto propionamide or Ν, Ν '-dihydrocarbyl dithiophosphate dipropyl acidamide reacts in the relatively low solvent of hydrogen chloride solubility (preferably 1 fat subsitutes hydrocarbon, 1 generation aromatic hydrocarbons or aliphatic hydrocarbon) with chlorination reagent.
U.S. Patent No. 5,453,507 discloses preparation Ν, Ν '-dimethyl-or Ν, Ν, the method for-di-n-octyl -4- isothiazoline -3- ketone, including makes Ν, and Ν '-dibasic dithio dipropyl acidamide exists
The organic solvent of halogenation（Such as CH2X2、 CHX3、 CX3CH3、 CHX2CHX2) in chlorosulfuric acid react.
However, the use of organic solvent causes problems in the above method.On the one hand, the use of solvent reduces the unit volume utilization rate of reactor, and then reduces productivity ratio；On the other hand, use, post processing and the recovery of solvent add production cost；Another aspect, the use of solvent may introduce other impurity, make the separation of product and purify more complicated；Another further aspect, organic solvents in particular be aromatic hydrocarbons and！Use for hydrocarbon pollutes the environment, and increases environmental pressure.The content of the invention
The purpose of the present invention is that the existing N- isothiazolinone derivatives preparation methods replaced are improved, and reduces its production cost, reduces environmental pollution.
On the one hand, the invention provides the preparation method of compound of Formula I,
Wherein R1Selected from alkyl, cycloalkyl and aryl, and R1On can further be selected from the substituent group of alkyl, aryl, alkoxy and aryloxy group；
R2And R3Hydrogen or chlorine independently are,
Methods described includes：
Under conditions of without using solvent, make Compounds of formula II,
Wherein R1It is defined as described above,
Or compound of formula III,
Wherein R1It is defined as described above,
With υ acyl chloride reactions.
In a preferred embodiment, R1Selected from CrC8Alkyl, C3-C8Cycloalkyl and C6-C10Aryl, and R1On can further be selected from CrC8Alkyl, C6-C1()Aryl, d-C8Alkoxy and C6-C1()The substituent group of aryloxy group.It is further preferred that R1Can be CrC8Alkyl, and R1Can be further by C6-C1QAryl or CrC8Alkoxy replaces.
In another preferred embodiment of the present, R2And R3It can be hydrogen simultaneously or while be chlorine.
Preferably, the reaction is about -10.C to about 75.Carried out at a temperature of C, more preferably in room temperature to about 45.C is carried out.
The inventive method, without using solvent, so as to avoid the various problems caused by using organic solvent, reduces production cost, reduces environmental pollution when preparing the isothiazolinone derivatives of N- substitutions. ·
On the other hand, the invention provides the preparation method of logical formula (III) compound, including：In methanol solvate, formula IV compound is made,
Reacted with compounds of formula V,
H2N—— 1(V) wherein R1It is defined as described above.
In a preferred embodiment, the mol ratio of the reaction compound of formula IV and compounds of formula V is about 1:2.0-2.6.Reaction temperature is preferably from about -15.C to about 65 ° (.
Simplify separation and the purge process of product<Embodiment
As described above, one aspect of the present invention provides the preparation method of the isothiazolinone derivatives of the N- substitutions shown in formula I,
Wherein R1Selected from alkyl, cycloalkyl and aryl, and R1On can further be selected from the substituent group of alkyl, aryl, alkoxy and aryloxy group；
R2And R3Hydrogen or chlorine independently are,
Methods described includes：
Under conditions of without using solvent, the 3-mercaptopropionyl amine for replacing the N- shown in formula II,
Wherein R1It is defined as described above,
Or Ν, Ν shown in general formula III ,-dibasic 3,3 ,-dithio dipropyl acidamide,
Wherein R1It is defined as described above,
With u acyl chloride reactions.
" alkyl " of the present invention is often referred to the saturated fat alkyl of straight or branched, is preferably
C o alkyl, more preferably（^-€8Alkyl, such as Yue bases, ethyl, n-propyl, isopropyl, normal-butyl, isobutyl group, the tert-butyl group, n-pentyl, n-hexyl, n-heptyl, n-octyl etc..
" cycloalkyl " of the present invention is often referred to the alicyclic hydrocarbon radical of saturation.Preferably C3-C1QCyclic hydrocarbon radical, more preferably C3-C8Cyclic hydrocarbon radical, such as cyclopropyl, cyclobutyl, cyclopenta etc..
" aryl " of the present invention is often referred to aromatic hydrocarbyl, preferably C6-C2.Aryl, more preferably C6-C1()Aryl, such as phenyl and Cai Ji, more preferably phenyl.
" without using solvent " of the present invention refers to except reaction beyond the region of objective existence, does not add other materials for being used to dissolve reactant, intermediate or final product additionally.
Chlorosulfuric acid is both as reactant in the inventive method, and is used as the solvent of initial reaction stage.As reaction is carried out, after chlorosulfuric acid runs out of, then to react the isothiazolinone derivatives generated as reaction dissolvent, thus other organic solvents need not be added.
In specific embodiments of the present invention, target product can be separated and purified by known technology, including but not limited to recrystallization and solvent extraction.
In a preferred embodiment, R1For-C8Alkyl, and R1Can be by C6-C1QAryl or CrC8Alkoxy replaces.It is highly preferred that R1For CrC8Alkyl, particularly preferably n-octyl.
In another preferred embodiment of the present, R2And R3It is hydrogen or while is chlorine simultaneously.
In the certain preferred embodiments of the present invention, methods described includes making logical formula (II) compound and ^ Τ υ acyl chloride reactions.It is highly preferred that logical formula (II) compound and the mol ratio of υ acyl chlorides are about 1:1-11.
In other embodiments of the present invention, in addition to chlorosulfuric acid, chlorine can be also used simultaneously as chlorination reagent.
In a preferred embodiment, the inventive method includes：Arbitrarily in the presence of chlorine, logical formula (III) compound is set to be reacted with chlorosulfuric acid.It is highly preferred that the mol ratio of logical formula (III) compound, chlorosulfuric acid and chlorine is about 1:1-11 :0-11.It is particularly preferred that the mol ratio of logical formula (III) compound, chlorosulfuric acid and chlorine is about 1:1-3:5-7.
In a particularly preferred embodiment, the inventive method also includes the step Sudden for preparing logical formula (III) compound, and the step includes：
In Yue alcoholic solvents, make the 3 of formula IV, 3, the Yue esters of-dithiodipropionic acid two,
(IV)
Reacted with the amine shown in formula V,
H2N— R1(V) wherein R1It is defined as described above.
Especially it is particularly preferred that formula IV compound and the mol ratio of compounds of formula V are about 1:2.0-2.6.Reaction temperature is preferably from about -15.C to about 65 °C, even more preferably about 5 °C are arrived room temperature.Reaction time is about 3 hours to about 5 days.
Another aspect provides the method for preparing compound of formula III, including：In Yue alcoholic solvents, make the 3 of formula IV, 3 ,-dithio dipropyl dimethyl phthalate,
Reacted with the amine shown in formula V,
H2N—— R1(V) wherein R1It is defined as described above.
Preferably, R1For CrC8Alkyl, and R1Can be by C6-C1()Aryl or CrC8Alkoxy replaces.It is highly preferred that R1For CrC8Alkyl, particularly preferably n-octyl.
It is preferred that the mol ratio of formula IV compound and formula V compounds is about 1 in the reaction:2.0-2.6.Reaction temperature is preferably from about -15.C to about 65 °C, even more preferably about 5 °C are arrived room temperature.Reaction time is about 3 hours to about 5 days.
In the methods of the invention, it because methanol is also simultaneously formula IV compound and the reaction product of compounds of formula V, therefore can avoid by solvent of Yue alcohol introducing other impurity, simplify separation and the purge process of product.Particularly with using water compared with the situation of solvent, of reaction product
Grain increase, so as to be easy to separate with mother liquor.Reaction mother liquor is reusable, and Yue alcohol is easy to be recovered by distillation, and reduces waste discharge.Embodiment
The preferred embodiments of the invention are described in detail hereinafter with reference to specific embodiment, it is to be understood that the present invention is not limited to these specific embodiments.Embodiment 1
N, N,-di-n-octyl -3,3,-dithio dipropyl acidamide to prepare reaction equation as follows：
(SCH2CH2C02CH3)2 + 2C8H17NH2 - (SCH2CH2CONHC8H17)2 + 2CH3OH adds 300ml methanol in 1000ml reaction bulbs, is subsequently added (1 mole of 238g）3,3 ,-dithio dipropyl dimethyl phthalate and 280g (2.17 moles) n-octyl amine, 5.Stirring reaction 5 days under C (：Protected if necessary with nitrogen）.Reactant mixture is cooled to -10.C, centrifuges out Ν, Ν,-di-n-octyl -3,3,-dithio dipropyl acidamide solid 329g (purity> 95./0, yield 76%) the reaction mother liquor way of distillation reclaim methanol Posterior circle use.
Embodiment 1
N- n-octyl-isothiazolin ketone（Including N- n-octyl -4- isothiazoline -3- ketone (OIT)
With N- n-octyls _4,5_ dichloro _4_ isothiazoline _3_ ketone (DCOIT)) to prepare reaction equation as follows：
(SCH2CH2CONHC8H17)2 + S02C12 + Cl2 ——►
(OIT) (DCOIT) adds chlorosulfuric acid 200ml (330g, 2.44 moles in 1000ml reaction bulb）, stir and be gradually added in lower 6.5 hours！^, 1^,-di-n-octyl -3,3,-dithio dipropyl acidamide 6488 (1.5 moles, per hour about 100g).Start to be passed through chlorine after 3 hours, 50g is passed through per hour and continues 13 hours, altogether (9.15 moles of about 650g）.Reactant mixture is voluntarily warming up to 40.Cooled after C using brine-cooled, keep reaction temperature in 40-45.C.Chlorine continues to maintain like temperature stirring 2 hours after the completion of being passed through.
With 50 in another 1000ml reaction bulb.Reactant mixture obtained by C hot wash is to faintly acid, if necessary with the acid in sodium acid carbonate with excess.With recrystallizing methanol, 190g DCOIT (Pure degree ＞ 95%) are obtained.OIT and DCOIT contained in recrystallization mother liquor is separated with methanol fractional extraction with petroleum ether, OIT 61g (purity is obtained>93%, yield 19%) and DCOIT 49g (purity>95%), DCOIT yields total 56.5%.
Although the certain preferred embodiments and embodiment of the present invention described in detail above, but those skilled in the art should be understood, various modifications and replacement can be carried out to embodiment of the present invention on the premise of essence spirit of the present invention and scope is not departed from, and these modifications and replacement all should be included in the equivalency range of the present invention.
Claims (1)
- Claims1. the preparation method of compound of Formula I,Wherein R1Selected from CrC8Alkyl ,-cycloalkyl and C6-C1()Aryl, and R1On can further be selected from CrC8Alkyl, C6-C1()Aryl, CrC8Alkoxy and C6-C1()The substituent group of aryloxy group；R2And R3Hydrogen or chlorine independently are,Methods described includes：Under conditions of without using solvent, make Compounds of formula II,It is therein defined as described above,Or compound of formula III,Wherein R1It is defined as described above,With u acyl chloride reactions.2. the method as described in claim 1, wherein R1For CrC8Alkyl, and R1Can further by-.Aryl or d-C8Alkoxy replaces.3. method as claimed in claim 2, wherein R1For CrC8Alkyl.4. method as claimed in claim 3, wherein R2And R3It is hydrogen or while is chlorine simultaneously.5. the method as described in any claim in claim 1-4, wherein the reaction is in -10 ° ~ 75 °C progress.6. the method as described in claim 5, wherein methods described include making formula (Π) compound react with chlorosulfuric acid, and logical formula (II) compound and the mol ratio of chlorosulfuric acid are about 1:1-11.7. method as claimed in claim 5, wherein methods described include：Arbitrarily in the presence of chlorine, make logical formula (III) compound and ^ acyl chloride reactions, and the mol ratio of logical formula (III) compound, chlorosulfuric acid and chlorine is about 1:1-11:0-11.8. method as claimed in claim 7, wherein methods described also include preparing the step Sudden of logical formula (III) compound, the step Sudden includes：In Yue alcoholic solvents, make formula IV compound,Reacted with compounds of formula V,H2N—— R1(V) wherein R1It is defined as described above.9. method as claimed in claim 8, wherein the formula IV compound and the mol ratio of compounds of formula V are about 1:2.0-2.6.10. method as claimed in claim 9, wherein the reaction of the formula IV compound and compounds of formula V is in -15 ° ~ 65 °C progress.11. the method for logical formula (III) compound is prepared,Wherein： R1Selected from CrC8Alkyl, C3-C8Cycloalkyl and C6-C1()Aryl, and R1On can further be selected from CrC8Alkyl, C6-C1QAryl, CrC8Alkoxy and C6-C1()The substituent group of aryloxy group,Methods described includes：In Yue alcoholic solvents, make formula IV compound,0II-S— CH2—— CH2— C— 0— CH (IV)Reacted with compounds of formula V,¾N—— R1(V) wherein R1It is defined as described above.12. method as claimed in claim 11, wherein the mol ratio of the formula IV compound and formula V compounds is about 1:2.0-2.6.13. the method as described in claim 11 or 12, wherein the reaction of the formula IV compound and compounds of formula V is -15.~ 65 °C of progress.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/CN2006/000590 WO2007112613A1 (en) | 2006-04-03 | 2006-04-03 | Preparation of n-substituted isothiazolinone derivatives |
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| Publication Number | Publication Date |
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| CN101218216A true CN101218216A (en) | 2008-07-09 |
| CN101218216B CN101218216B (en) | 2010-08-25 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN2006800247050A Expired - Fee Related CN101218216B (en) | 2006-04-03 | 2006-04-03 | Preparation of N-substituted isothiazolinone derivatives |
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| Country | Link |
|---|---|
| US (2) | US7893273B2 (en) |
| JP (1) | JP4889737B2 (en) |
| KR (1) | KR101017031B1 (en) |
| CN (1) | CN101218216B (en) |
| CH (1) | CH697358B1 (en) |
| WO (1) | WO2007112613A1 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102002015A (en) * | 2010-09-10 | 2011-04-06 | 大连星原化学有限公司 | Air-borne preparation method for isothiazolinone and derivants thereof |
| CN112159365A (en) * | 2020-10-13 | 2021-01-01 | 大连百傲化学股份有限公司 | Method for co-producing OIT and DCOIT |
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| CN101417966A (en) * | 2007-10-25 | 2009-04-29 | 北京天擎化工有限责任公司 | Continuous production method of 3-isothiazolone derivates |
| WO2010113857A1 (en) * | 2009-03-31 | 2010-10-07 | ナガセケムテックス株式会社 | Microbicide |
| JP5871800B2 (en) * | 2010-08-11 | 2016-03-01 | 協和メデックス株式会社 | Method for measuring glycated hemoglobin |
| WO2012031407A1 (en) * | 2010-09-10 | 2012-03-15 | 大连星原化学有限公司 | Preparation method of isothiazolinone and derivatives thereof in gas carrier |
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| CN103570642B (en) * | 2012-08-01 | 2015-03-18 | 中国中化股份有限公司 | Isothiazolinone compound and application thereof as bactericide |
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| CN106588810A (en) * | 2016-11-29 | 2017-04-26 | 大连九信精细化工有限公司 | Method for deeply chlorinating cauldron bottom residues of 2-octyl-3(2H)-isothiazolone |
| CN112110870B (en) * | 2020-09-28 | 2022-06-03 | 大连百傲化学股份有限公司 | Preparation method of 2-methyl-4-isothiazoline-3-ketone aqueous solution |
| CN112110871A (en) * | 2020-11-03 | 2020-12-22 | 大连百傲化学股份有限公司 | Preparation method of 3-isothiazolinone compound |
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- 2006-04-03 KR KR1020087002734A patent/KR101017031B1/en not_active IP Right Cessation
- 2006-04-03 CN CN2006800247050A patent/CN101218216B/en not_active Expired - Fee Related
- 2006-04-03 WO PCT/CN2006/000590 patent/WO2007112613A1/en active Application Filing
- 2006-04-03 US US11/997,963 patent/US7893273B2/en not_active Expired - Fee Related
- 2006-04-03 CH CH01859/07A patent/CH697358B1/en not_active IP Right Cessation
- 2006-04-03 JP JP2008523100A patent/JP4889737B2/en not_active Expired - Fee Related
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102002015A (en) * | 2010-09-10 | 2011-04-06 | 大连星原化学有限公司 | Air-borne preparation method for isothiazolinone and derivants thereof |
| CN102002015B (en) * | 2010-09-10 | 2013-05-01 | 大连星原化学有限公司 | Air-borne preparation method for isothiazolinone and derivants thereof |
| CN112159365A (en) * | 2020-10-13 | 2021-01-01 | 大连百傲化学股份有限公司 | Method for co-producing OIT and DCOIT |
| CN112159365B (en) * | 2020-10-13 | 2022-05-20 | 大连百傲化学股份有限公司 | Method for co-producing OIT and DCOIT |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101218216B (en) | 2010-08-25 |
| US8927735B2 (en) | 2015-01-06 |
| US7893273B2 (en) | 2011-02-22 |
| KR20080026639A (en) | 2008-03-25 |
| US20080227986A1 (en) | 2008-09-18 |
| CH697358B1 (en) | 2008-08-29 |
| US20110112327A1 (en) | 2011-05-12 |
| KR101017031B1 (en) | 2011-02-23 |
| WO2007112613A1 (en) | 2007-10-11 |
| JP2009502814A (en) | 2009-01-29 |
| JP4889737B2 (en) | 2012-03-07 |
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